Experimental modification of cerebellar development in tissue culture

What is it about?

Cerebellum explants from 15--16 day fetal mice were irradiated with 500--1000 tad X-ray and were grown in tissue culture for 12--18 days. At the dose of 500 tad, a reduction of granule cell population was observed in the explant. At the dose of 1000 rad, granule cells were mostly destroyed leaving Purkinje cells disarrayed and clustered. Electron microscopy of the explants revealed the presence of unattached dendritic spines of Purkinje cell. It was noted that although numerous free spines could be seen in X-irradiated cultures, the postsynaptic specialization of these spines occurred only in ones embedded in astrocytic cytoplasm. The results indicate that (a) the formation of dendritic spines is a property of the Purkinje cell which probably is preprogrammed and (b) the postsynaptic differentiation of the unattached spines is directly related to their contacts with astrocytes.

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Why is it important?

The presence of unattached spines in various conditions has been the subject of extensive speculation in terms of interpretation of their origin and significance. In cases of destruction of the granule cells and their axons in adult animals the unattached spines could represent the persistent postsynaptic component of a previously well-developed axon-dendritic synapse, as it has been observed elsewhere in the CNS and the peripheral nervous system. This hypothesis cannot be used in the interpretation of the presence of the unattached spines in the X-irradiated fetal cerebellum cultures, where synapses between the Purkinje cells and granule cells have not developed yet, as it is well established that those synapses are formed in the mouse cerebellum postnatally. It is important that in the present study, we observed that although numerous free Purkinje cell dendritic spines could be seen in the absence of parallel fibers or of any other presynaptic components, the postsynaptic specialization of these spines occurred only in ones embedded in the astrocytic perikaryon or surrounded by the processes of astrocytes. This observation leads to the concept that (a) the formation of Purkinje cell dendritic spines is a property of the Purkinje cell, which probably is preprogrammed and (b) the postsynaptic differentiation of the unattached spines is directly related to their contacts with astrocytes, since the membrane thickening and the aggregation of electron dense material at the interior surface of the plasma membrane of the spine has so far been seen only in spines in contact with astrocytes. This observation suggests that the astrocyte in addition of its role in isolating synaptic contacts , probably plays an important role in the synaptogenesis.

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